Coronary artery calcium clinical utilization: An update.

Coronary artery calcium (CAC) scoring by computed tomography (CT) has been the subject of intense interest and critical scrutiny since it was first reported as a clinical tool in 1990.1 With improvements in study design, greater availability of coronary CT scanners, and increased attention to the posttest prognosis of patient samples and asymptomatic individuals who have undergone coronary CT, CAC measurement is now considered a potentially useful test for improving coronary risk assessment in selected intermediate-risk asymptomatic patients in whom high CAC scores signify increased cardiovascular risk beyond that predicted by conventional cardiovascular risk factors alone.2 Article p 1693 At the other end of the spectrum, does a very low CAC score signify very low risk? An American Heart Association writing group3 stated that a CAC score of zero (CAC=0; ie, no calcified plaque detected) indicated 1) that the presence of atherosclerotic plaque, including unstable or vulnerable plaque, was highly unlikely; 2) that the presence of significant luminal obstructive disease was highly unlikely (negative predictive value on the order of 95% to 99%); and 3) that the risk of a cardiovascular event in the next 2 to 5 years was quite low (0.1 per 100 person-years). In addition, at least 1 early study suggested that CAC=0 might be useful in the emergency room setting as a tool to rule out myocardial ischemia in symptomatic patients.4 A recent review article5 suggested the same conclusions. However, as pointed out by a different …

Calcifications are part of the development of atherosclerosis; they occur exclusively in atherosclerotic arteries and are absent in the normal vessel wall.1 Studies have demonstrated calcification in both coronaries and aortic arteries to be a specific marker of underlying atherosclerosis in the respective vascular beds.1 Extensive evidence exist that men are more likely to have calcification in the coronary arteries2,3; however, whether similar difference exists in other vascular beds is not well established. The purpose of this study is to evaluate whether the lower risk of atherosclerosis observed in coronary circulation in women compared with men is also observed in thoracic aorta. This is a cross-sectional study on a consecutive sample of 8549 asymptomatic individuals (69% men, mean age: 52±9 years) patients who presented to a single EBT scanning facility for CHD risk stratification.4 A history of cigarette smoking was considered present if a subject was a current or former smoker. Dyslipidemia was coded as present for any individual self-reporting a history of high total cholesterol, high LDL, low HDL, and/or high triglycerides, or current use of lipid-lowering therapy. Patients were considered to have diabetes if they reported using oral hypoglycemic agents, insulin sensitizers, or subcutaneous insulin and hypertension if they reported a history of high blood pressure or used antihypertensive medications. A family history of CHD was considered premature if the immediate family (parents or siblings) experienced a fatal or nonfatal myocardial infarction before age of 55 years. Individuals …

The U.S. multi-societal chest pain guideline – A quick look into a long-awaited document

Article, see p 1993 The clinician now has an overwhelming array of investigations at his or her disposal for patients with suspected coronary heart disease. These tests are used to diagnose or risk-stratify patients and thereby enable the clinician to treat their symptoms and reduce their future risk. Ultimately, these investigations either assess risk factors (eg, lipid, glucose, and C-reactive protein concentrations) and proxies for disease (eg, carotid intima-media thickness and coronary artery calcium score) or are looking to provide circumstantial downstream evidence of disease (eg, markers of ischemia and infarction: Q waves on an ECG, fibrosis on magnetic resonance imaging or functional stress testing). In this issue of Circulation , Budoff and colleagues1 compare 2 of the most widely used approaches, coronary artery calcium scoring and functional stress testing, within the framework of the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Coronary artery calcification is considered pathognomonic of atherosclerosis and has been a marker of coronary artery disease for millennia.2 Its presence is, however, a proxy of disease because it is induced in response to atherosclerosis, and, apart from rare calcific nodules, calcification does not directly cause ischemic heart disease events. Indeed, calcification appears to be an adaptive healing response to the necrotic atheromatous plaque whereby the body attempts to limit and contain the disease, much like the calcification of a caseating granuloma from mycobacterium tuberculosis infection. However, calcification does not directly relate to the degree of luminal or functional stenosis of the coronary artery, nor does it necessarily reflect the current status of the plaque because the calcification may be inactive, ongoing, or incomplete. Indeed, large areas of inert macrocalcification are associated with plaque stability, whereas spotty calcifications or microcalcifications are associated with high-risk plaques, probably because of incomplete calcification.3– …

Association of Lipoprotein Subfractions and Coronary Artery Calcium In Patient at Intermediate Cardiovascular Risk

PET/CT imaging of myocardial blood flow and arterial calcium: Putting the pieces together

With completion of the human genome sequence, expectations are rising that a detailed catalogue will soon be available of all important common genetic susceptibility variants for human diseases, including coronary heart disease (CHD) and related atherosclerotic cardiovascular disease (CVD).1 In light of this seminal event in medical research, it is curious that the family history of CHD has not been accorded a more central role in risk prediction and disease prevention by clinicians and public health professionals. A positive family history of CHD is present in the majority of cases of premature-onset CHD.2 In cases of familial hypercholesterolemia and other rare forms of premature-onset CVD, CHD clearly segregates in a mendelian fashion. For most cases of premature-onset CHD, the mode of genetic transmission in families is less clear. Although the family history of CHD has been considered a putative risk factor for decades, it has not been incorporated along with other established risk factors such as hyperlipidemia, hypertension, and cigarette smoking in some widely applied multivariable risk algorithms,3 though other risk algorithms do incorporate family history information.4 See p 2150 This cautious approach to widespread application of family history information is not due to insufficient evidence. Risks for CHD death are greatest in monozygotic (identical) compared with dizygotic (nonidentical) twins, particularly when there is a premature (eg, <65 years) age of onset in the initially affected twin.5 In multiple prospective studies involving hundreds of thousands of men and women, a parental history of premature CHD is a significant risk factor for CVD even after multivariable adjustment. Relative risk estimates generally range from 1.2 to 2.0, as noted in the Physician’s Health Study and Women’s Health Study,6 although the estimated magnitude of risk associated with early-onset parental disease is substantially higher in some studies.7 …

C ardiac computed tomography (CT) and positron emis- sion tomography (PET) are emerging as powerful noninvasive imaging tools for the evaluation of atherosclerosis in patients with known or suspected coronary artery disease (CAD).Unlike invasive coronary angiography, CT coronary angiography (CTA) not only assesses disease within the coronary lumen but can also provide direct qualitative and quantitative information about nonobstructive atherosclerotic plaque burden within the vessel wall.Thus, it is possible that CTA-based patient evaluation may provide more clinically relevant information on which to base risk assessments compared with conventional "lumenography."On the other hand, PET is rapidly growing as a powerful and efficient alternative to conventional single-photon emission CT (SPECT) imaging to evaluate regional myocardial perfusion and metabolism in patients with CAD.In addition, PET scanners are now being converted to hybrid PET/CT devices, which, in the setting of CAD, offer the potential for a comprehensive noninvasive cardiac evaluation of anatomy and function.This review will discuss current and potential future applications of cardiovascular CT, PET, and hybrid PET/CT, with a particular focus on ischemic heart disease.

Improved Coronary Risk Assessment With Electron Beam Computed Tomography in an Asymptomatic Female With Familial Hypercholesterolemia

This scientific statement reviews the scientific data for cardiac computed tomography (CT) related to imaging of coronary artery disease (CAD) and atherosclerosis. Cardiac CT is a CT imaging technique that accounts for cardiac motion, typically through the use of ECG gating. The utility and limitations of generations of cardiac CT systems are reviewed in this statement with emphasis on CT measurement of CAD and coronary artery calcified plaque (CACP) and noncalcified plaque. Successive generations of CT technology have been applied to cardiac imaging beginning in the early 1980s with conventional CT, electron beam CT (EBCT) in 1987, and multidetector CT (MDCT) in 1999. Compared with other imaging modalities, cardiac CT has undergone an accelerated …

Effect of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue Volume and Coronary Vasomotor Function

Subclinical Atherosclerosis and Relationship With Risk Factors of Coronary Artery Disease in a Rural Population

Background: Coronary artery calcification (CAC) and carotid intima-media thickness (CIMT), established measures of subclinical atherosclerosis, that have been demonstrated to improve prediction of coronary artery disease (CAD) risk beyond classical risk factors (CRFs). This study examined the epigenetic mechanisms underlying the appearance of CAC and increased CIMT, which have not been previously explored. Methods: We conducted an epigenome-wide association study (EWAS) in 46 non-smoking and non-diabetic white subjects randomly selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CAC and CIMT were measured by computed tomography (CT) and catotid artery ultrasound at examination year (Y) 20. The Illumina HumanMethylation450 BeadChip was used to measure DNA methylation in white blood cells collected at Y15. We dropped one sample with &gt;1% of the CpG sites having a detection p-value &gt;0.05 and then exclude ~160k CpG probes due to their ambiguously mapping to the genome or with the presence of common SNPs, etc. Both background adjustment and normalization were performed separately for Infinium I and II probes, and new values were calculated and then transformed into M-values. After correction for potential chip effect, we examined the associations between these pre-processed methylation levels at each CpG site with CAC and CIMT using multiple logistic and linear regression models, respectively. Pathway analysis was performed to explore the gene sets that were significantly associated with CAC and CIMT. Results: Several CpG sites in multiple genes were significantly associated with CAC or CIMT. Some of these genes play roles in the regulation of vascular function, such as ion binding and transport ( HRH1 , LRP1B , KCNJ9 , TRIM40 , ADAMTS3 for CAC and BRSK2 , ZNF428 , TROVE2 , C1orf86 for CIMT) and metabolic processes ( LEPR for CAC and NUP50 for CIMT). Pathway analyses revealed several common canonical pathways for CAC and CIMT including, calcium signaling, axon guidance, and focal adhesion etc., which are relevant to the occurrence of these two subclinical CADs. The statistical significance of identified CpG sties for either CAC or CIMT did not remain after correction for multiple testing, possibly due to the small sample size. Conclusion: Our preliminary findings suggest that methylomic mechanisms may play a role in the development of CAC and CIMT, and subsequently the etiology of CAD. Future replication studies in larger longitudinally studies are needed.

This editorial refers to ‘Pre-screening to guide coronary artery calcium scoring for early identification of high-risk individuals in the general population’, by D. Ties et al., https://doi.org/10.1093/ehjci/jeac137. Coronary artery calcium (CAC) is a marker of atheromatous epicardial coronary artery disease, with the exception of chronic kidney disease, which can cause coronary calcification without appreciable atherosclerosis.1 CAC can be imaged directly with non-contrast, electrocardiogram-gated computed tomography (CT) and has been proven to have both diagnostic and prognostic value.2 Its clinical use is recommended by contemporary practice guidelines in individuals with an intermediate cardiovascular risk, e.g. a Systemic COronary Risk Estimation (SCORE2) of 5–10%, rather than in persons with a low or high risk.3,4 Non-imaging based risk stratification (e.g. with SCORE2) may not be accurate on an individual level; therefore, its use as a gatekeeper for deciding on CT CAC is currently a topic of discussion. In the current issue of the journal, Ties5 investigated the ability of a standard risk score (SCORE2) to identify individuals with a high CAC from a large population not known with coronary artery disease. CT CAC was measured in 6530 individuals participating in the Lifeline study: a large, population-based cohort and biobank originating in The Netherlands. The study population was stratified by CAC, and the focus was on patients with CAC ≥100 and patients with CAC ≥300. SCORE2, however, missed 32% of individuals with a CAC ≥300 when using a ≥5% threshold, and 41% of persons with a CAC ≥100 using the same threshold. Similarly, SCORE2 failed to identify 81 and 87% of individuals with CAC ≥300 and CAC ≥100 respectively, when screening for those individuals with a higher risk (≥10%). Routinely used clinical risk scores such as SCORE2, therefore missed a significant number of persons with CAC scores which are known to be associated with worse outcomes, suggesting that application of such risk scores (as a gatekeeper for individuals who should undergo CAC CT for further risk stratification) is an insensitive approach.

Introduction Coronary clearance in patients undergoing TAVR is performed by invasive coronary angiography (ICA) or computed tomography angiography (CTA). We aimed to investigate whether CTA-derived low coronary calcium (CAC) score may rule out obstructive coronary artery disease (CAD) in these patients. Methods We included 232 consecutive patients with severe aortic stenosis (mean age 80±8; 50% female) who underwent both pre-TAVR CTA and ICA between 2012–2019. Obstructive CAD was defined as a &amp;gt;50% in left main or &amp;gt;70% in the 3 main epicardial vessels. Patients with prior coronary stents or bypass grafts were excluded. CAC score was calculated by Agatston method. Receiver operating characteristic (ROC) was applied to establish the CAC threshold for obstructive CAD, and adjustment for age, gender, diabetes and renal failure was applied. Results CAC scores range was 3.5–5200 (median = 1028). Eighty-eight patients (38%) had obstructive CAD. ROC curves showed high negative predictive value (NPV) for LAD - CAC score 280, NPV 95%; LCX - CAC score 320, NPV 93%; and RCA - CAC score 347, NPV 90% (figure). Binary logistic regression confirmed CAC score cutoffs per vessel as an independent predictor of obstructive CAD [LAD (OR 3.9, CI 1.1–14, p-0.033); CX (OR 5.7, CI 2.4–12, p&amp;lt;0.001); RCA (OR-5.6, CI 2.5–12, p&amp;lt;0.001)]. Conclusion CAC score per-vessel can be useful to rule out obstructive CAD in patients with severe aortic stenosis undergoing TAVR. Using specific CAC cut offs can identify patients who may omit ICA CAC per vessel Funding Acknowledgement Type of funding source: None